The acute respiratory distress syndrome (ARDS) is a serious clinical problem. It occurs as a sequelae to other serious illnesses, often multiple traumas. ARDS is difficult to study in human patients because of the variability of patient populations. Multiple traumas are difficult to model in animal preparations because of variability of injury and humane considerations since most forms of trauma are associated with pain. ARDS is not commonly seen in people with burn injury alone, but some 20% of patients who sustain thermal trauma develop ARDS, usually as a result of inhalation of smoke. This research summary points out the complexity of the problems related to ARDS especially that form of the syn-drome associated with burn injury and smoke inhalation. It also illustrates the contribution to that knowledge that has been made by co-investigators of this proposal. Given the successful collaboration of our group, the unique models, facilities and techniques that we have developed together, our goals and objectives should be accomplished in this proposal. In addition to the understanding of the cascade of events that comprise the development of ARDS, the proposal should also test efficacy of several therapeutic interventions and when they would be effective in clinically relevant models. Although we do not describe any human studies in our proposal, many of the co-investigators are prominent clinicians actively involved in daily clinical care of burned patients at two of the major burn units in the world. Consequently, the findings of our proposal can be rapidly tested in patient populations. Finally, given the present interactions of this group of investigators, the laboratory and clinical environment in which they work, pathophysiological interactions and therapeutic interventions that were not described in the proposal are very likely to develop during the duration of the proposal.